<strong>Discussed the Application of Curcumin Combined with Piperine Based on the Metabolic Characteristics of Curcumin</strong>

Abstract

Abstract:

Curcumin is a yellow acid phenolic substance with anti-tumor，anti-oxidation， anti-inflammatory and anti-fibrosis pharmacological effects，but its low bioavailability has always limited the development and utilization of curcumin. Piperine and cinnamolphthalein alkaloids have good safety，and can increase the bioavailability of curcumin by inhibiting multiple drug metabolic enzymes and transporters，thus increasing its pharmacological effects in many aspects. Using new preparation technology to encapsulate curcumin and piperine in special carrier materials can endow drugs with new properties，such as increased solubility，improved stability and drug targeting，so as to further increase the therapeutic effect of curcumin.The aim of this paper is to summarize the molecular and metabolic characteristics of curcumin，to discuss the mechanism of piperine increasing its pharmacological action from the metabolic perspective， and to summarize the research status of combined use of curcumin and piperine，so as to provide reference for future scientific research.

Key words:curcumin,piperine,combination therapy,bioavailability

CLC Number:

R964

LIANG Yu-fei，ZHANG Xin-xin，ZHAO Li-yan，et al.Discussed the Application of Curcumin Combined with Piperine Based on the Metabolic Characteristics of Curcumin[J]. Acta Neuropharmacologica,DOI: 10.3969/j.issn.2095-1396.2019.06.010.

References

[1] 国家药典委员会. 中华人民共和国药典(一部)[M]. 中国医药科技出版社，2015，265.
[2] Neha Verma, Surbhi Bal, Ranjan Gupta, et al. Antioxidative effects of piperine against cadmium-induced oxidative stress in cultured humanperipheral blood lymphocytes[J]. J Diet Suppl, 2018, 10(9): 1-12.
[3] Sonia Siddiqui, Aiman Kanwal, Khawar Saeed Jamali, et al. Piperine attenuates the cancerous activity response in Neuro-2a cell line[J]. Pak J Pharm Sci, 2018, 31(4Suppl): 1529-1538.
[4] Ma Zhen-guo, Yuan Yu-pei, Zhang Xin, et al. Piperine attenuates pathological cardiac fibrosis via PPAR-γ/AKT pathways[J]. EBioMedicine, 2017, 4(18): 179-187.
[5] Chen Wang-sheng, Jie An, Li Jian-jun, et al. Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia[J]. Int Immunopharmacol, 2017, 1(42): 44-48.
[6] Wang Xi-ting, Sun Xue-jiao, Li Cheng, et al. Establishing a cell-based high-content screening assay for TCM compounds with anti-renal fibrosis effects[J]. Evid Based Complement Alternat Med, 2018, 7942614.
[7] Anchi Pratibha, Khurana Amit, Debasish Swain, et al. Dramatic improvement in pharmacokinetic and pharmacodynamic effects of sustain release curcumin microparticles demonstrated in experimental type 1 diabetes model[J]. European J Pharmaceutical Sciences, 2019, 15(130): 200-214.
[8] Bo Wahlstrom, Blennow G A. A study on the fate of curcumin in the rat[J]. Acta. Pharmacologica Et Toxicologica, 1978, 43(2): 86–92.
[9] Vijayalaksmi Ravindranath, Nanajundiah Chandrasekhara. Metabolism of curcumin--studies with [3H]curcumin [J]. Toxicology, 1981, 22(4): 337-344.
[10] Vijayalakshmi Ravindranath, Nanjundiah Chandrasekhara. Absorption and tissue distribution of curcumin in rats[J]. Toxicology, 1980, 16(3): 259-265.
[11] Shaiju K Vareed, Madhuri Kakarala, Mack T Ruffin IV, et al. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects[J]. Cancer Epidemiology Biomarkers & Prevention, 2008, 17(6): 1411-1417.
[12] Elham Gholibegloo, Tohid Mortezazadeh, Fatemeh Salehian, et al. Improved curcumin loading, release, solubility and toxicity by tuning the molar ratio of cross-linker to β-cyclodextrin[J]. Carbohydr Polym, 2019, 213: 70-78.
[13] Mahesh Kharat, Du Zhe-yuan, Zhang Guo-dong, et al. Physical and chemical stability of curcumin in aqueous solutions and emulsions: impact of ph, temperature, and molecular environment[J]. J Agric Food Chem, 2017, 65(8): 1525-1532.
[14] Takanori Tsuda. Curcumin as a functional food-derived factor: degradation products, metabolites, bioactivity, and future perspectives[J]. Food Funct, 2018, 9(2), 705-714.
[15] Wang Ruo-ning, Han Jia-wei, Jiang Ai, et al. Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine[J]. Int J Pharm, 2019, 561: 9-18.
[16] Pradnya Bapat, Rohan Ghadi, Dasharath Chaudhari, et al. Tocophersolan stabilized lipid nanocapsules with high drug loading to improve the permeability and oral bioavailability of curcumin[J]. Int J Pharm, 2019, 560: 219-227.
[17] Mohammad N Oskouie, Nazanin S Aghili Moghaddam, Alexandra E Butler, et al. Therapeutic use of curcumin-encapsulated and curcumin-primed exosomes[J]. J Cell Physiol, 2019, 234(6): 8182-8191.
[18] Susmita Bose, Naboneeta Sarkar, Dishary Banerjee. Effects of PCL, PEG and PLGA polymers on curcumin release from calcium phosphate matrix for in vitro and in vivo bone regeneration[J]. Mater Today Chem, 2018, 8: 110-120.
[19] Huang Rong, Han Jia-wei, Wang Ruo-ning, et al. Surfactant-free solid dispersion of BCS class IV drug in an amorphous chitosan oligosaccharide matrix for concomitant dissolution in vitro - permeability increase[J]. Eur J Pharm Sci, 2019, 130: 147-155.
[20] Hamed Mirzaei, Abolfazl Shakeri, Bahman Rashidi, et al. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies[J]. Biomed Pharmacother, 2017, 1(85): 102-112.
[21] Griet Dewitte, Maarten Walmagh, Margo Diricks, et al. Screening of recombinant glycosyltransferases reveals the broad acceptor specificity of stevia UGT-76G1[J]. J Biotechnol, 2016, 233: 49-55.
[22] Chen Bin-lin, Chen Yan-qiu, Ma Bai-hui, et al. Tetrahydrocurcumin, a major metabolite of curcumin, ameliorates allergic airway inflammation by attenuating Th2 response and suppressing the IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2 -Notch1/Notch2 pathways in asthmatic mice[J]. Clin Exp Allergy, 2018, 48(11): 1494-1508.
[23] Huang Yi-yuan, Cao Shi-jie, Zhang Qiang, et al. Biological and pharmacological effects of hexahydrocurcumin, a metabolite of curcumin[J]. Arch Biochem Biophys, 2018, 5(646): 31-37.
[24] Simone I Hoehle, Erika Pfeiffer, Manfred Metzler. Glucuronidation of curcuminoids by human microsomal and recombinant UDP-glucuronosyl transferases[J]. Mol Nutr Food Res, 2007, 51(8): 932-938.
[25] Takashi Isobe, Susumu Ohkawara, Sadayuki Ochi, et al. Naringenin glucuronidation in liver and intestine microsomes of humans, monkeys, rats, and mice[J]. Food Chem Toxicol, 2018, 1(111): 417-422.
[26] Timothy H Marczylo, Richard D Verschoyle, Darren N Cooke, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine[J]. Cancer Chemother Pharmacol, 2007, 60(2): 171-177.
[27] Dhivya Velumani, Lohanathan Bharathi Priya, Hilda T Chirayil, et al. Piperine modulates isoproterenol induced myocardial ischemia through antioxidant and anti-dyslipidemic effect in male Wistar rats[J]. Biomed Pharmacother, 2017, 3(87): 705-713.
[28] Siddiqui S, Kanwal A, Jamali KS, et al. Piperine attenuates the cancerous activity response in Neuro-2a cell line[J]. Pak J Pharm Sci, 2018, 31(4Suppl): 1529-1538.
[29] Ma Zhen-guo, Yuan Yu-pei, Zhang Xin, et al. Piperine attenuates pathological cardiac fibrosis via PPAR-γ/AKT pathways[J]. E Bio Medicine, 2017, 4(18): 179-187.
[30] Chen Wang-Sheng, Jie An, Li Jian-Jun, et al. Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia[J]. Int Immunopharmacol, 2017, 1(42): 44-48.
[31] Yue-Ming Wang, Wenwei Lin, Sergio C Chai, et al. Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1[J]. Toxicol Appl Pharmacol, 2013, 272(1): 96–107.
[32] Bhargavi Athukuri Latha, Prasad Neerati. Enhanced oral bioavailability of domperidone with piperine in male wistar rats: involvement of CYP3A1 and P-gp inhibition[J]. J Pharm Pharm Sci, 2017, 20(1): 28-37.
[33] Vaisgali M Patil, Sukanya Das, Krishnan Balasubramanian. Quantum chemical and docking insights into bioavailability enhancement of curcumin by piperine in pepper[J]. J Phys Chem A, 2016, 120(20): 3643-3653.
[34] Carolyn Doucette, Gemma Rodgers, Robert S Liwski, et al. Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes[J]. J Cell Biochem, 2015, 116(11): 2577-2588.
[35] Pawinee Piyachaturawat, Thirayudh Glinsukon, Chaivat Toskulkao. Acute and subacute toxicity of piperine in mice, rats and hamsters[J]. Toxicol Lett, 1983, 16(3-4): 351-359.
[36] Guido Shoba, David Joy, Thangam Joseph, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers[J]. Planta Med, 1998, 64(4): 353-356.
[37] Pbd Suresh, Krishnapura Srinivasan. Tissue distribution & elimination of capsa icin, piperine & curcumin following oral intake in rats[J]. Indian J Med Res, 2010, 131(5): 682-691.
[38] Vaishali M Patil, Sukanya Das, Krishnan Balasubramanian. Quantum chemical and docking insights into bioavailability enhancement of curcumin by piperine in pepper[J]. Phys Chem A, 2016, 120(20): 3643–3653.
[39] Durg Vijay Singh, Madan M Godbole, Krishna Misra. A plausible explanation for enhanced bioavailability of P-gp substrates in presence of piperine: simulation for next generation of P-gp inhibitors[J]. J Mol Model, 2013, 19(1): 227-238.
[40] Tang Jing-ling, Ji Hong-yu, Ren Jin-mei, et al. Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro[J]. Oncol Lett, 2017, 13(1): 389–395.
[41] Li Sen, Lei Yu, Jia Ying-jie, et al. Piperine, a piperidine alkaloid from Piper nigrum re-sensitizes P-gp, MRP1 and BCRP dependent multidrug resistant cancer cells[J]. Phytomedicine, 2011, 19(1): 83-87.
[42] Shimaa Ashmawy, Sanaa A El-Gizawy, Gamal El Maghraby, et al. Regional difference in intestinal drug absorption as a measure for the potential effect of P-glycoprotein efflux transporters[J]. J Pharm Pharmacol, 2019, 71(3): 362-370.
[43] Jin Zhao-hui, Qiu Wen, Liu Hui, et al. Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine[J]. Chin J Nat Med, 2018, 16(2): 143-149.
[44] Li Chen-rui, Wang Zhi-jun, Wang Qian, et al. Enhanced anti-tumor efficacy and mechanisms associated with docetaxel-piperine combination- in vitro and in vivo investigation using a taxane-resistant prostate cancer model[J]. Oncotarget, 2017, 9(3): 3338-3352.
[45] Cook D J, Finnigan J D, Cook K, et al. Cytochromes P450: history, classes, catalytic mechanism, and industrial application[J]. Adv Protein Chem Struct Biol, 2016, 105: 105-126.
[46] Martin Klingenberg. Pigments of rat liver microsomes[J]. Arch Biochem Biophys, 1958, 75(2): 376-386.
[47] Dalvi R R, Dalvi P S. Comparison of the effects of piperine administered intragastrically and intraperitoneally on the liver and liver mixed-function oxidases in rats[J]. Drug Metabol Drug Interact, 1991, 9(1): 23-30.
[48] Dalvi R R, Dalvi P S. Differences in the effects of piperine and piperonyl butoxide on hepatic drug-metabolizing enzyme system in rats[J]. Drug Chem Toxicol, 1991, 14(1-2): 219-229.
[49] Rashmeet K Reen, Jaswant Singh. In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine, a major ingredient of piper species[J]. Indian J Exp Biol, 1991, 29(6): 568-573.
[50] Suhaili Shamsi, Huong Tran, Renee Siok Jin Tan, et al. Curcumin, piperine, and capsaicin: a comparative study of spice-mediated inhibition of human cytochrome P450 isozyme activities[J]. Drug Metab Dispos, 2017, 45(1): 49-55.
[51] Nattharat Jaerapong, Qurratul Ain Jamil, Juliane Riha, et al. Organic anion transporting polypeptides contribute to the uptake of curcumin and its main metabolites by human breast cancer cells: Impact on antitumor activity[J]. Oncol Rep, 2019, 41(4): 2558-2566.
[52] Shintu Jude, Augustine Amalraj, Ajaikumar Kunnumakkara, et al. Development of Validated Methods and Quantification of Curcuminoids and Curcumin Metabolites and Their Pharmacokinetic Study of Oral Administration of Complete Natural Turmeric Formulation (Cureit™) in Human Plasma via UPLC/ESI-Q-TOF-MS Spectrometry[J]. Molecules, 2018, 23(10): E2415.
[53] Kiyotaka Nakagawa, Takahiro Harigae, Taiki Miyazawa, et al. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration[J]. Int J Nanomedicine, 2016, 11: 3009-3022.
[54] Pbd Suresh, Krishnapura Srinivasan. Influence of curcumin, capsaicin, and piperine on the rat liver drug-metabolizing enzyme system in vivo and in vitro[J]. Can J Physiol Pharmacol, 2006, 84(12): 1259-1265.
[55] Atal C K, Dubey R K, Jaswant Singh. Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism[J]. J Pharmacol Exp Ther, 1985, 232(1): 258-262.
[56] Yui Kau Fong, Li Chen-rui, Siu Kwan Wo, et al. In vitro and in situ evaluation of herb–drug interactions during intestinal metabolism and absorption of baicalein[J]. J Ethnopharmacol, 2012, 141(2): 742-753.
[57] Rashmeet K Reen, Deshvir S Jamwal, Subhash C Taneja, et al. Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine[J]. Biochem Pharmacol, 1993, 46(2): 229-238.
[58] Jaswant Singh, Dubey R K, Atal C K. Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content[J]. J Pharmacol Exp Ther, 1986, 236(2): 488-493.
[59] Ashok Jangra, Mohit Kwatra, Tavleen Singh, et al. Piperine augments the protective effect of curcumin against lipopolysaccharide-induced neurobehavioral and neurochemical deficits in mice[J]. Inflammation, 2016, 39(3): 1025-1038.
[60] Shamsher Singh, Puneer Kumar. Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats[J]. Inflammopharmacology, 2017, 25(1): 69-79.
[61] Shamsher Singh, Puneet Kumar. Neuroprotective activity of curcumin in combination with piperine against quinolinic acid induced neurodegeneration in rats[J]. Pharmacology, 2016, 97(3-4): 151-160.
[62] Shamsher Singh, Sumit Jamwal, Puneet Kumar. Piperine enhances the protective effect of curcumin against 3-np induced neurotoxicity: possible neurotransmitters modulation mechanism[J]. Neurochem Res, 2015, 40(8): 1758-1766.
[63] Puneet Rinwa, Anil Kumar, Sukant Garg. Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression[J]. PLoS One, 2013, 8(4): e61052.
[64] Li Yong-nan, Li Min, Wu Shuo-dong, et al. Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: whether NPC1L1/SREBP2 participates in this process?[J]. Lipids Health Dis, 2015, 14(1): 100.
[65] Tu Yao-sheng, Sun Dong-mei, Zeng Xiao-hui, et al. Piperine potentiates the hypocholesterolemic effect of curcumin in rats fed on a high fat diet[J]. Exp Ther Med, 2014, 8(1): 260-266.
[66] Amit Sehgal, Manoj Kumar, Maeghal Jain, et al. Modulatory effects of curcumin in conjunction with piperine on benzo(a)pyrene-mediated DNA adducts and biotransformation enzymes[J]. Nutr Cancer, 2013, 65(6): 885-890.
[67] A Sehgala, M Kumara, M Jaina, et al. Combined effects of curcumin and piperine in ameliorating benzo(a)pyrene induced DNA damage[J]. Food Chem Toxicol, 2011, 49(11): 3002-3006.
[68] Amit Sehgal, Manoj Kumar, Mridula Jain, et al. Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced redox imbalance in mice lungs[J]. Toxicol Mech Methods, 2012, 22(1): 74-80.
[69] Amit Sehgal, Manoj Kumar, Maeghal Jain, et al. Piperine as an adjuvant increases the efficacy of curcumin in mitigating benzo(a)pyrene toxicity[J]. Hum Exp Toxicol, 2012, 31(5): 473-482.
[70] Yunes Panahi, Nahid Khalili, Ebrahim Sahebi, et al. Effects of curcuminoids plus piperine on glycemic, hepatic and inflammatory biomarkers in patients with type 2 diabetes mellitus: a randomized double-blind placebo-controlled trial[J]. Drug Res (Stuttg), 2018, 68(7): 403-409.
[71] Yunes Panahi, Nahid Khalili, Ebrahim Sahebi, et al. Curcuminoids plus piperine modulate adipokines in type 2 diabetes mellitus[J]. Curr Clin Pharmacol, 2017, 12(4): 253-258.
[72] Christine Tara Peterson, Alexandra R Vaughn, Vandana Sharma, et al. Effects of turmeric and curcumin dietary supplementation on human gut microbiota: a double-blind, randomized, placebo-controlled pilot study[J]. J Evid Based Integr Med, 2018, 23: 2515690X18790725.
[73] Manodeep Chakraborty, Bhattacharjee A, Kamath JV. Cardioprotective effect of curcumin and piperine combination against cyclophosphamide-induced cardiotoxicity[J]. Indian J Pharmacol, 2017, 49(1): 65-70.
[74] Barthelemy Delecroix, Abd- Elbasset Abaïdia, Cedric Leduc, et al. Curcumin and piperine supplementation and recovery following exercise induced muscle damage: a randomized controlled trial[J]. J Sports Sci Med, 2017, 16(1): 147-153.
[75] Laurie P Volak, Michael J Hanley, Gina Masse, et al. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers[J]. Br J Clin Pharmacol, 2013, 75(2): 450-462.
[76] Wang Jun-peng, Sally M Vanegas, Du Xiao-gang, et al. Caloric restriction favorably impacts metabolic and immune/inflammatory profiles in obese mice but curcumin/piperine consumption adds no further benefit[J]. Nutr Metab (Lond), 2013, 10(1): 29.
[77] Livia Hlava?ková, Andrea Janegová, Olga Uli?ná, et al. Spice up the hypertension diet - curcumin and piperine prevent remodeling of aorta in experimental L-NAME induced hypertension[J]. Nutr Metab (Lond), 2011, 8: 72.
[78] Preeti S Chauhan, Anju Jaiswal, Subhashini, et al. Combination therapy with curcumin alone plus piperine ameliorates ovalbumin-induced chronic asthma in mice[J]. Inflammation, 2018, 41(5): 1922-1933.
[79] Zeng Xiao-hui, Cai Dake, Zeng Qiao-huang, et al. Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat[J]. Biopharm Drug Dispos, 2017, 38(1): 3-19.
[80] Li Qiu-ping, Dai Jun-dong, Zhai Wen-wen, et al. Optimization and characterization of curcumin-piperine dual drug loaded self-microemulsifying drug delivery system by simplex lattice design[J]. Zhongguo Zhong Yao Za Zhi, 2014, 39(20): 3936-3944.
[81] Li Qiu-ping, Zhai Wen-wen, Jiang Qiao-li, et al. Curcumin–piperine mixtures in self-microemulsifying drug delivery 2 system for ulcerative colitis therapy[J]. Int J Pharm, 2015, 490(1-2): 22-31.
[82] Tang Jing-ling, Ji Hong-yu, Ren Jin-mei, et al. Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro[J]. Oncol Lett, 2017, 13(1): 389-395.
[83] Chutima Jantarat, Pornpak Sirathanarun, Somruedee Boonmee, et al. Effect of piperine on skin permeation of curcumin from a bacterially derived cellulose-composite double-layer membrane for transdermal curcumin delivery[J]. Sci Pharm, 2018, 86(3): E39.
[84] Tu Y S, Fu J W, Sun D M, et al. Preparation, characterisation and evaluation of curcumin with piperine-loaded cubosome nanoparticles[J]. J Microencapsul, 2014, (6): 551-559.
[85] Yucel Baspinar, Mehmet Üstündas, Oguz Bayraktar, et al. Curcumin and piperine loaded zein-chitosan nanoparticles: Development and in-vitro characterisation[J]. Saudi Pharm J, 2018, 26(3): 323-334.
[86] Juthamas Ratanavaraporn, Sorada Kanokpanont, Siriporn Damrongsakkul. The development of injectable gelatin/silk fibroin microspheres for the dual delivery of curcumin and piperine[J]. J Mater Sci Mater Med, 2014, 25(2): 401-410.
[87] Annu Khajuria A, Thusu N, Zutshi U. Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: influence on brush border membrane fluidity, ultrastructure and enzyme kinetics[J]. Phytomedicine, 2002, 9(3): 224-31.
[88] Rakesh Johri, Thusu N, Annu Khajuria, et al. Piperine-mediated changes in the permeability of rat intestinal epithelial cells. The status of gamma-glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation[J]. Biochem Pharmacol, 1992, 43(7): 1401-1407.

Discussed the Application of Curcumin Combined with Piperine Based on the Metabolic Characteristics of Curcumin

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